tbuckley/cabot-search huggingface dataset:
Is a ‘cancer check-up’ near for high-risk adults? clinician attitudes and perspectives on multicancer early detection tests.
Authors: Tariqa Ackbarali, Catherine Marinac, Tomasz M. Beer
Journal: Journal of Clinical Oncology (2022)

e23008 Background: Current screening guidelines for many cancers are limited and multiple cancer-screening tests are not yet FDA approved. The development and potential use of a pan-tumor or multi-cancer early detection (MCED) test has been met with both enthusiasm and hesitation, despite its potential for early detection and a resultant reduction in cancer-related mortality and morbidity. The lack of knowledge of clinician perceptions of MCED test and the need to educate a multidisciplinary team prompted the design of educational initiatives in 2020 and 2021. Methods: In September 2020 and July 2021; two 1-hour CME activities were launched live-online on OMedLive.com; the 2021 activity remains on-demand until July 2022. The 2020 activity introduced the value proposition and trial designs of MCED tests and reviewed the current cancer screening guidelines. Challenges revealed from the 2020 activity informed the multidisciplinary approach of the 2021 activity presenting epidemiology, oncology, and primary care perspectives. In both activities, participants were assessed at 3 time points (pre-, immediate post-, and 2 mos. post-activity) and McNemar tests compared paired responses with Cohen’s d for effect size. Behavioral impact, perception, and practice pattern questions were also assessed immediately post-activity and year-to-year data analyzed. Results: As of 02/13/22, 1,015 clinicians have participated in the 2020 activity and 3,372 in the 2021 activity. Across the eight CME test questions, seven exhibited improvements in knowledge/competence related to screening modalities, trial data, value of MCED tests, and clinical workflow following results. In the analysis of perception and practice pattern questions, 50% of clinicians were likely to integrate MCED tests into their practice; however, expectation of high costs and access/availability to utilize MCED tests at their practice were the top barriers identified. A lack of consensus in identifying adults at higher risk of cancer was observed in 2020 with improvements seen in 2021. At 2-mos. follow-up for the 2020 and 2021 activity, respectively, clinicians reported practice behavior changes as 89% and 73% related to clinical practice, while 89% and 72% reported improved patient experience/outcomes. Qualitative data including clinician write-in examples of specific practice behavior changes will be analyzed. Conclusions: These data provide real-world insight into clinician perspectives on MCED tests and the clinical, patient-care, and workflow challenges that should be considered before incorporating future approaches on multi-cancer screening. As the primary care setting is most suited for the introduction of novel cancer-screening tools, PCPs and oncologists will require continued education to apply practical strategies for point-of-care decision-making and transitions of care protocols.
Impact of hospital volume on the outcomes of renal trauma management
Authors: P. Baloche, N. Szabla, L. Freton, M. Hutin, M. Ruggiero, I. Dominique, C. Millet, S. Bergerat, P. Panayotopoulos, R. Betari, X. Matillon, A. Chebbi, T. Caes, P-M. Patard, N. Brichart, C. Dariane, M. Baboudjian, B. Gondran-Tellier, C. Lebacle, F-X. Madec, F-X. Nouhaud, X. Rod, G. Fiard, B. Pradere, B. Peyronnet
Journal: European Urology (2022)
Awareness of risk of prostate cancer (PCa) remains poor in families with germline mutations in DNA-repair genes
Authors: G. Chiarelli, V. Fasulo, M. Zuradelli, N. Buffi, G. Lughezzani, G. Guazzoni, C.B. Ripamonti, A. Benetti, P. Casale, A. Saita, R. Hurle, P.P. Avolio, M. Lazzeri
Journal: European Urology (2022)
Efficacy and safety profile of antivascular endothelial growth factor receptor tyrosine kinase inhibitors (avRTKIs) in patients (Pts) with neuroendocrine tumors(NETs): A systematic review and meta-analysis (SRMA).
Authors: Satya Das, Sharon E. Phillips, Cody L Lee, Heather E. Laferriere, Rajiv Agarwal, Robert A. Ramirez, Jordan Berlin, Arvind Dasari
Journal: Journal of Clinical Oncology (2022)

e16216 Background: Vascular endothelial growth factor mediated signaling is central to NETs. As such, multiple avRTKIs have been tested in NETs over the last 2 decades, mostly in small phase II studies. In fact, there have been no randomized phase III trials conducted in United States apart from the one leading to approval of sunitinib in pancreatic (p) NETs. Several other avRTKIs have demonstrated clinical promise including surufatinib in phase III trials conducted in China; this drug is currently under FDA review for potential approval. In the current SRMA, we aim to address this deficiency by benchmarking efficacy and safety profiles of avRTKIs. Methods: A literature search was done to identify all phase II and phase III studies of avRTKIs in pts with NETs published between 1/1/2000–7/31/2021. Data abstraction was performed by one author and validated by another. Efficacy was assessed by aggregating progression-free survival (PFS) and overall response rate (ORR) data. PFS and ORR were assessed using a random effects model separately for pts with pNETs and extra-pancreatic (ep) NETs. Toxicity was assessed by calculating the relative risk (RR) compared to control arm and incidence of adverse events (AEs) of interest. Results: Of 92 identified studies, 17 (with 8 individual avRTKIs) were included in the meta-analysis after excluding redundant studies; baseline study characteristics are listed in the Table.A total of 1611 pts (853 men, 758 women) were available for the analysis; 1194 received avRTKIs. The ORR in pNETs was 18% (95% confidence interval (CI) 13-25%) while the ORR in pts with epNETs was 8% (95% CI 5-12%); test for differences between pNETs and epNETs (x 1 2 = 8.47, p &lt; .01). The median PFS in pNETs was 13.9 months (95% CI 11.43-16.38 months) while median PFS in epNETs was 12.71 months (95% CI 9.37-16.05 months); test for differences between pNETs and epNETs (x 1 2 = .32, p = .57). The incidence (and RR compared to control) of most common ≥ grade 3/4 AEs were hypertension 22.4% (4.48, p &lt; .001), diarrhea 6.4% (RR 3.03, p = .005), neutropenia 5.2% (20.4, p = .036) and proteinuria 4.6% (27.25, p = .001). Incidence (and RR compared to control) of rare but serious complications included non-central nervous system bleeding 8.7% (2.17, p &lt; .001) and cardiac dysfunction 6.4% (2.52, p = .01). Conclusions: Among pts tx with avRTKIs, pts with pNETs demonstrated improved ORR but not PFS compared to these outcomes in pts with epNETs. In addition, this study also benchmarks the incidence and RR of AEs in pts with NETs treated with avRTKIs who are often on therapy longer than other pts.[Table: see text]
Heterogeneity of tumor immune microenvironment and real-world analysis of immunotherapy efficacy in lung adenosquamous carcinoma.
Authors: Xiaobin Zheng, Gen Lin, Xinlong Zheng, Feng Long, Kan Jiang, Tony S. K. Mok
Journal: Journal of Clinical Oncology (2022)

e20546 Background: Lung adenosquamous carcinoma (ASC) is an uncommon histological subtype. We aimed to characterize the tumor immune microenvironment (TIME) in lung ASC and estimate patient response to immune checkpoint inhibitors (ICIs), which have never been systematically investigated. Methods: In cohort I, we collected 30 ASCs from a single center for analysis of TIME characteristics, including immuno-phenotyping, tumor mutation burden (TMB), T cell receptor (TCR) repertoires, tumor-infiltrating lymphocytes (TILs), and immune checkpoint expression. In cohort II, the efficacy of ICI-based therapy were estimated using a real-world data of 46 ASCs from 11 centers. Results: In cohort I, 22 (73.3%) patients were EGFR-positive. The TIME were defined by immune-excluded (60%) and immune-desert phenotype (40%). Strikingly, PD-L1 and PD-1 were predominantly expressed in SCCC versus ACC, where enhanced CD4 + FOXP3 + regulatory T cell and attenuated CD57 + natural killer cell infiltration was present, consistent with a landscape of fewer innate immune cells, more immunosuppressive cells. SCCC had higher TMB, higher TCR clonality, and lower TCR diversity than ACC. In cohort II, majority of 46 patients were driver genes negative and unknown mutation status, 18 (39%) and 18 (39%), respectively. Overall objective response rate of 28%, median progression-free survival of 6.0 months (95% CI 4.3-7.7), and median overall survival of 24.7 months (95% CI 7.2-42.2) were observed in the ICI-based treatment. Conclusions: This work ascertains suppressive TIME in lung ASC and genetic and immuno-heterogeneity between ACC and SCCC. Lung ASC patients have a moderate response to ICI-based immunotherapy.
Hemolysis, free hemoglobin toxicity, and scavenger protein therapeutics
Authors: Florence Vallelian, Paul W. Buehler, Dominik J. Schaer
Journal: Blood (2022)

During hemolysis, erythrophagocytes dispose damaged red blood cells. This prevents the extracellular release of hemoglobin, detoxifies heme, and recycles iron in a linked metabolic pathway. Complementary to this process, haptoglobin and hemopexin scavenge and shuttle the red blood cell toxins hemoglobin and heme to cellular clearance. Pathological hemolysis outpaces macrophage capacity and scavenger synthesis across a diversity of diseases. This imbalance leads to hemoglobin-driven disease progression. To meet a void in treatment options, scavenger protein-based therapeutics are in clinical development.
Caloric restriction reduces the pro-inflammatory eicosanoid 20-hydroxyeicosatetraenoic acid to protect from acute kidney injury
Authors: Karla Johanna Ruth Hoyer-Allo, Martin Richard Späth, Susanne Brodesser, Yiyi Zhu, Julia Binz-Lotter, Martin Höhne, Hella Brönneke, Katrin Bohl, Marc Johnsen, Torsten Kubacki, Katharina Kiefer, Lisa Seufert, Felix Carlo Koehler, Franziska Grundmann, Matthias J. Hackl, Bernhard Schermer, Jens Brüning, Thomas Benzing, Volker Burst, Roman-Ulrich Müller
Journal: Kidney International (2022)
EPCT-09. ROVER: A phase 1/2 study of avapritinib in pediatric patients with solid tumors dependent on KIT or PDGFRA signaling
Authors: Susan Chi, Antony Hsieh, Megan Foley, Hongliang Shi, Preethi Swamy, Jill Rodstrom, Marc Rudoltz
Journal: Neuro-Oncology (2022)

Abstract Prognosis for pediatric patients with advanced relapsed/refractory (R/R) solid (including central nervous system [CNS]) tumors is poor. KIT alterations are common in germ cell tumors and high-grade glioma (HGG); platelet-derived growth factor receptor alpha (PDGFRA) alterations are common in sarcoma and HGG. H3K27M-mutant gliomas are dependent on PDGFRA signaling. No KIT/PDGFRA targeted therapies are currently approved for pediatric patients with R/R solid or CNS tumors, or H3K27M-mutant gliomas. Selective KIT and PDGFRA inhibitor avapritinib demonstrated potent activity against KIT activation-loop (exon 17), juxtamembrane (exon 11), and extracellular-domain (exon 9) mutants (IC50&amp;lt;2 nM), and PDGFRA activation-loop (D842V) mutants (IC50=0.24 nM); cellular IC50 of PDGFRA wild-type was 95 nM. CNS penetration in preclinical models (steady-state brain-to-plasma ratios ranging from 0.74–1.00) has demonstrated potential for CNS antitumor activity. Avapritinib is approved in the USA to treat adults with unresectable/metastatic gastrointestinal stromal tumors (GIST) harboring PDGFRA exon 18 mutations (including D842V), and adults with advanced systemic mastocytosis. In the EU, avapritinib is approved for adults with unresectable/metastatic GIST harboring a PDGFRA D842V mutation. Objectives of ROVER 2-part phase 1/2, multicenter, open-label study (NCT04773782) are avapritinib safety, preliminary efficacy, and pharmacokinetics in pediatric patients aged 2 to &amp;lt;18 years with solid R/R tumors dependent on KIT or PDGFRA signaling, including H3K27M-mutant gliomas, and no alternative treatment options. Part 1 will enroll ≥12 patients; primary endpoint is confirmed age and body surface area physiologically based pharmacokinetic modeling predicted dose to provide equivalent exposure to the 300 mg adult avapritinib dose. Part 2 will enroll ≥25 patients at the recommended avapritinib dose from Part 1; the primary endpoint is objective response rate. Avapritinib once-daily will be administered in continuous 28-day cycles. Enrollment in this study is planned at 26 sites in 10 countries, including centers in North America, Europe, and Asia/Pacific.
Evaluation of the Molecular Landscape of Pediatric Thyroid Nodules and Use of a Multigene Genomic Classifier in Children
Authors: Jean-Nicolas Gallant, Sheau-Chiann Chen, Carlos A. Ortega, Sarah L. Rohde, Ryan H. Belcher, James L. Netterville, Naira Baregamian, Huiying Wang, Jiancong Liang, Fei Ye, Yuri E. Nikiforov, Marina N. Nikiforova, Vivian L. Weiss
Journal: JAMA Oncology (2022)

Importance Definitive diagnosis of a thyroid nodule in a child is obtained through diagnostic surgery. This is problematic because pediatric thyroid surgery is associated with higher rates of complications. In adults, preoperative molecular testing improves the management of thyroid nodules, but this has not been validated in children. Objective To determine whether the molecular landscape of pediatric thyroid nodules is amenable to detection by a multigene genomic classifier (GC) test (ThyroSeq v3; Sonic Healthcare USA). Design, Setting, and Participants This was a retrospective consecutive case series and GC testing of fine-needle aspiration (FNA) and formalin-fixed paraffin-embedded (FFPE) tissues from sequential pediatric thyroidectomies performed between January 2003 and December 2019 at a single tertiary academic medical center. The study included 95 patients (median [range] age, 16.3 [4.8 to 21.1] years; 75 [79%] female) who underwent surgery for a thyroid nodule. Interventions A total of 118 thyroid nodule samples (95 FFPE, 23 companion FNAs) yielded informative next-generation sequencing data and multigene GC. Main Outcomes and Measures The primary outcome was the determination of the pediatric thyroid molecular landscape. The secondary outcome was the diagnostic accuracy of the GC test for pediatric thyroid nodules. Results Of the 95 patients, 75 (79%) were female, and the median (IQR) age was 16.3 (14.0-17.3) years. Next-generation sequencing confirmed the unique molecular landscape of malignant pediatric thyroid nodules (compared with adults), which is dominated by gene fusions (most commonly RET and NTRK ), rare BRAF / RAS alterations, and no TP53 or TERT promoter pathogenic variants. Several poorly differentiated thyroid cancers harbored DICER1 variants. Benign nodules appeared to be almost exclusively associated with TSHR and DICER1 alterations. The test demonstrated a 96% sensitivity (95% CI, 87%-99%) and 78% specificity (95% CI, 64%-88%). The negative predictive value was 95% (95% CI, 88%-98%) and the positive predictive value was 83% (95% CI, 74–89%). The concordance of GC between 23 pairs of matched FFPE and FNA tissues was 96%. Conclusions and Relevance The study results of this retrospective consecutive case series suggest that the molecular landscape of pediatric nodules is unique but remains amenable to molecular classification. The multigene GC test, with high sensitivity and reasonably high specificity, represents a potential addition to the diagnostic workup of children with thyroid nodules and may decrease the use of diagnostic surgery.
Feasibility of 68Ga-FAPI-46 PET/CT for detection of metastatic spread in urothelial carcinoma
Authors: L.M. Unterrainer, S. Lindner, L. Eismann, J. Casuscelli, F-J. Gildehaus, N.V. Bui, N.L. Albert, A. Holzgreve, A. Todica, M. Brendel, L. Beyer, C.C. Cyran, A. Karl, C.G. Stief, S.T. Ledderose, M. Unterrainer, P. Bartenstein, V. Wenter, A. Kretschmer
Journal: European Urology (2022)
Cost effectiveness of adjuvant olaparib for BRCA-mutated, early-stage breast cancer.
Authors: Christie Zettler, Dilanka De Silva, Victoria Susana Blinder, Mark E. Robson, Elena B. Elkin
Journal: Journal of Clinical Oncology (2022)

6593 Background: An interim analysis of the OlympiA trial found that olaparib given in the adjuvant setting can improve distant disease-free and overall survival for patients with early-stage, BRCA-mutated breast cancer; however, the cost-effectiveness of adjuvant olaparib is unknown. This study aimed to evaluate the cost-effectiveness of adjuvant olaparib in patients with early-stage, BRCA-mutated breast cancer. Methods: We used a decision-analytic model to compare outcomes of treatment with and without one year of oral olaparib after completion of systemic therapy in 42-year-old women with BRCA-mutated, early-stage breast cancer. Olaparib’s effectiveness was based on the OlympiA trial, and other model parameters were identified from the literature. We calibrated the model to reflect the 1-, 2-, and 3-year distant disease-free survival (DDFS) and overall survival (OS) observed in the OlympiA trial, and we assumed that olaparib reduced the risk of distant recurrence only in the first 3 years. Olaparib was estimated to cost $14,523 per month. Average lifetime costs were estimated from a health care system perspective in 2021 $ US, and incremental cost-effectiveness ratios (ICER) were estimated as $ per quality-adjusted life-year (QALY) gained. Costs, life-years, and QALYs were discounted by 3% annually. Results: Simulating the OlympiA trial, DDFS for the olaparib arm was 94.3% at 12 months, 90.0% at 24 months, and 87.5% at 36 months, compared to placebo with DDFS of 90.2%, 83.9%, and 80.4% respectively. Similarly, OS for the olaparib arm was 98.1%, 94.8%, and 92.0% compared to 96.9%, 92.3%, and 88.3% with placebo at 12, 24, and 36 months respectively. In the base case, adjuvant olaparib was associated with a 1.21-year increase in life expectancy and a 1.15-QALY increase at an incremental cost of $131,167 compared to placebo. The resulting ICER was about $114,500/QALY gained. At a willingness-to-pay threshold of USD$150,000/QALY, olaparib was cost effective at its current price. Results were sensitive to assumptions about the effectiveness of olaparib and its impact on quality of life. Conclusions: Adjuvant olaparib is cost-effective for women with early-stage, BRCA-mutated breast cancer at the current price of olaparib in the U.S. and at a willingness-to-pay threshold of $150,000. As such, clinicians and payers should consider adjuvant olaparib as a cost-effective option for this patient population. [Table: see text]
Toripalimab combined with chemoradiotherapy for patients with locally advanced cervical squamous cell carcinoma.
Authors: Dan Ou, Haoping Xu
Journal: Journal of Clinical Oncology (2022)

5538 Background: To assess the safety and efficacy of toripalimab combined with chemoradiotherapy for locally advanced cervical squamous cell carcinoma (Chinese Clinical Trial Registry number, ChiCTR2000032879). Methods: Twenty-two locally advanced cervical cancer patients, regardless of programmed death ligand-1 status, received toripalimab treatment combined with concurrent chemoradiotherapy. Concurrent chemoradiotherapy(CCRT) includes cisplatin (40 mg/m2, once a week for 5 weeks), radiotherapy (external irradiation 45-50.4Gy/25-28Fx, 5 fractions a week, followed by brachytherapy 24-30Gy/3-5Fx) and toripalimab (240mg on days 1, 22 and 43). The primary end-point was safety and feasibility. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), overall survival (OS). Results: The median age was 55 years old (range, 42 to 72 years old), with 2 patients in FIGO stage II, 15 patients in stage IIIC, and 5 patients in stage IVA. All patients have received CCRT successfully. Grade III and higher adverse events (AEs) were observed in 10 patients (10/22, 45.5%), and no patient had a grade V AE. The most frequent grade III AE was leukopenia (8/22, 36.4%). The most common immunotherapy-related adverse reaction was hypothyroidism (2/22, 9.1%). The 3-month ORR rate was 95.5%. At data cutoff (Jan 31, 2022), the median follow-up was 10 months (range, 3.30 to 16.73 months). One patient developed multiple metastases 3 months after treatment, and 1 patient developed lung metastasis 6 months after treatment. The ORR was 100%, while the PFS rate was 90.1%, and the OS rate was 95.5%. Conclusions: Toripalimab combined with concurrent chemoradiotherapy demonstrated a manageable safety profile and promising anti-tumor activity in patients with locally advanced cervical cancer, thus might represent a novel treatment option for this patient population. Longer follow-up results and further phase II/III studies are expected. Clinical trial information: ChiCTR2000032879.
Factors associated with baseline quality of life in patients with oral cavity and oropharyngeal cancer.
Authors: Jie Deng, Barbara A. Murphy, Lucy Andersen, Mary S. Dietrich
Journal: Journal of Clinical Oncology (2022)

e18079 Background: Baseline quality of life (QOL) predicts for survival in head and neck cancer patients. The purpose of this study was to identify factors contributing to baseline QOL in patients with newly diagnosed oral cavity or oropharyngeal cancer (OCOPC) in order to identify potential targets for intervention. Methods: 115 patients with OCOPC completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, Hospital Anxiety and Depression Scale, and Brief Health Literacy Screen (BHLS). Pearson correlation and ANOVA statistics were used to analyze the data. Results: The median global health-related QOL score was 66.7 (IQR: 50, 83.4); 35.7% of participants reported anxiety and 18.3% reported depressive symptoms (HADS ≥8); 30.8% of patients had BHLS values of ≤ 9. Factors associated with significant decrease in global health-related QOL score: household income of &lt; $20,000/year (p = .010); low health literacy (p = .021); having symptoms of anxiety (p &lt; .001); having depressive symptoms (p &lt; .001); and non-HPV associated cancer (p &lt; .001). Increased tumor stage, older age, single/widowed marital status, and unemployment were associated with the lower scores on the physical QOL subscale (p &lt; .05). Increased tumor stage was associated with lower scores on role and social QOL subscales (p &lt; .05), and younger age was associated with lower scores on emotional QOL subscale (p &lt; .05). Conclusions: Baseline QOL is associated with socioeconomic and disease-related determinants. Clinical trial information: NCT02412241.